Abstract
Objective: This study was conducted to elucidate the long non-coding RNA FOXD2-AS1 (lncRNA FOXD2-AS1) expression in glioma and its mechanism on the biological features of glioma cells and the drug resistance of temozolomide (TMZ).Results: Highly expressed FOXD2-AS1 was found in glioma. There was more powerful chemotherapeutic resistance of TMZ resistant cell lines than that of the parent cell lines. Silence of FOXD2-AS1 suppressed proliferation and drug resistance and promoted apoptosis of drug-resistant glioma cells. Overexpressed FOXD2-AS1 presented an opposite trend. FOXD2-AS1 could be used as a competing endogenous RNA to adsorb miR-98-5p, thereby up-regulating CPEB4.Conclusion: Our study suggests that down-regulated FOXD2-AS1 repressed invasion, proliferation, migration and drug resistance of drug-resistant glioma cells while stimulating their apoptosis via increasing miR-98-5p and inhibiting CPEB4 expression.Methods: FOXD2-AS1, microRNA-98-5p (miR-98-5p) and cytoplasmic polyadenylation element binding (CPEB4) expression in glioma tissues were tested. Expression of E-cadherin, N-cadherin and Vimentin in glioma cells were explored. A series of assays were conducted to detect the function of FOXD2-AS1 in migration, proliferation, apoptosis, and invasion of glioma cells. Changes in drug-resistance of cells under TMZ treatment were examined, and tumor formation in nude mice was performed to test the changes of drug resistance in vivo.
Highlights
Glioma is the most common type of primary intracranial tumor, occupying 81% of malignant brain tumors, and it has high mortality and morbidity [1]
The relationship between FOXD2-AS1 expression and the clinicopathological characteristics of glioma patients was further analyzed, and it was found that the expression level of FOXD2AS1 was not associated with the gender, age and histological type of patients, but related to tumor diameter and World Health Organization (WHO) classification, lymph node metastasis and TMZ drug resistance (Table 1)
< 0.001 < 0.001 < 0.001 were varying degrees of higher expression of FOXD2AS1 in 4 kinds of glioma cells in contrast with HEB cells, of which FOXD2-AS1 was obviously expressed in the U87 and U251 cell lines, which were chosen for subsequent experiments
Summary
Glioma is the most common type of primary intracranial tumor, occupying 81% of malignant brain tumors, and it has high mortality and morbidity [1]. Glioblastoma (GBM) is the most malignant glioma subtype in adults; the survival time of patients with GBM is only around 15 months, making GBM one of the most invasive cancers [4]. Temozolomide (TMZ), a new oral imidazotetrazinone methylating agent, has a schedule-dependent antitumor activity in all types of late cancers, including malignant gliomas [5]. TMZ-based chemotherapy is a typical www.aging-us.com strategy for treatment of glioma, while chemo-resistance acts as a main therapeutic challenge [6]. Absence of obvious improvement of patient survival, developing drug resistance in recurrent tumor, and scarce alternative chemotherapy drugs are the main stumbling blocks for TMZ in glioma treatment [7]. Great achievements have been made in multimodality treatments including radiotherapy, chemotherapy, and surgical resection, the poor prognosis of GBM has not improved for more than three decades [8]. With glioma’s unclear diagnosis, poor prognosis, and limited treatment methods, it is urgent to seek new therapeutic targets to improve the prognosis of the disease
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